Gli effetti della scala Critical-Care Pain Observation Tool nella valutazione e gestione del dolore nei pazienti con lesioni cerebrali ricoverati in terapia intensiva

INTRODUCTION. Accurate pain assessment and management in critically ill patients withcognitive alterations who are unable to communicate constitute a major challenge for themedical and nursing staff of Intensive Care Units (ICUs). This study want assess the impact of Critical Care Pain Observation Tool (CCPOT) scale in ICU practice and evaluate the effects on pain assessment and management in brain-injured critically ill adult patients.  METHODS. This before-and-after study was carried out in an Italian ICU, where data were collected before (T0) and after (T1) implementation of the CCPOT in brain-injured critically ill adults.  RESULTS. The study population consisted of 81 patients (35 before and 46 after intervention). The use of propofol fell significantly (propofol: t(80) = 1.83, p =.03) and at the same time the use of morphine increase significantly (morphine: t(80) = 1.51, p =.02) after intervention.Analysis of the data with respect to pain relief and prevention during some nursing care activities revealed a significant increase in the use of fentanyl citrate (x2(1)= 4.04, p =.04) and paracetamol (x2(1)= 5.30, p =.02). Pain management was in line with the protocol, which envisaged administration of pain medications to patients with CCPOT scores > 3 in 76.8% of cases.  CONCLUSION. The present findings strongly support the value of the CCPOT scale in managing ICU patient pain in conjunction with medical and nursing staff training. However, further studies of larger patient samples should be performed. critiche con alterazioni cognitive non in grado di comunicare, costituiscono una grande sfida per il personale medico e infermieristico delle Terapie Intensive (TI). Questo studio vuole valutare l'impatto della scala CCPOT in TI, valutandone gli effetti sulla valutazione e gestione del dolore nei pazienti adulti con lesioni cerebrali.  METODI. Questo studio before-after è stato condotto in una terapia intensiva italiana, in cui i dati sono stati raccolti prima (T0) e dopo (T1) l'implementazione dello strumento.  RISULTATI. La popolazione di studio era composta da 81 pazienti (35 prima e 46 dopo l'intervento). L'uso di propofol è diminuito in modo significativo (propofol: t(80) = 1.83, p = .03) e allo stesso tempo, l'uso della morfina è aumentata in modo significativo (morfina: t(80) = 1,51, p = .02) dopo il nostro intervento. L'analisi dei dati relativi al sollievo dal dolore e alla prevenzione durante alcune attività di assistenza infermieristica ha rivelato un aumento significativo dell'uso di fentanil citrato (x2(1) = 4.04, p = .04) e paracetamolo (x2(1) = 5.30, p = .02). La gestione del dolore era in linea con il protocollo, che prevedeva la somministrazione di antidolorifici a pazienti con punteggi CCPOT > 3 nel 76.8% dei casi.  CONCLUSIONE. I risultati supportano fortemente il valore della scala CCPOT nella gestione del dolore dei pazienti in terapia intensiva unitamente alla formazione del personale medico einfermieristico. Tuttavia, devono essere eseguiti ulteriori studi su campioni di pazienti didimensioni maggiori.&nbsp

Osteoblast mineralization requires β1 integrin/ICAP-1–dependent fibronectin deposition

ICAP-1 prevents recruitment of kindlin-2 to β1 integrin to control dynamics of fibrillar adhesion sites, fibronectin deposition, and osteoblast mineralization during bone formation

PGF2α-F-prostanoid receptor signalling via ADAMTS1 modulates epithelial cell invasion and endothelial cell function in endometrial cancer

<p>Abstract</p> <p>Background</p> <p>An increase in cancer cell invasion and microvascular density is associated with a poorer prognosis for patients with endometrial cancer. In endometrial adenocarcinoma F-prostanoid (FP) receptor expression is elevated, along with its ligand prostaglandin (PG)F_2α, where it regulates expression and secretion of a host of growth factors and chemokines involved in tumorigenesis. This study investigates the expression, regulation and role of a disintegrin and metalloproteinase with thrombospondin repeat 1 (ADAMTS1) in endometrial adenocarcinoma cells by PGF_2αvia the FP receptor.</p> <p>Methods</p> <p>Human endometrium and adenocarcinoma tissues were obtained in accordance with Lothian Research Ethics Committee guidance with informed patient consent. Expression of ADAMTS1 mRNA and protein in tissues was determined by quantitative RT-PCR analysis and immunohistochemistry. Signal transduction pathways regulating ADAMTS1 expression in Ishikawa cells stably expressing the FP receptor to levels seen in endometrial cancer (FPS cells) were determined by quantitative RT-PCR analysis. In vitro invasion and proliferation assays were performed with FPS cells and human umbilical vein endothelial cells (HUVECs) using conditioned medium (CM) from PGF_2α-treated FPS cells from which ADAMTS1 was immunoneutralised and/or recombinant ADAMTS1. The role of endothelial ADAMTS1 in endothelial cell proliferation was confirmed with RNA interference. The data in this study were analysed by T-test or ANOVA.</p> <p>Results</p> <p>ADAMTS1 mRNA and protein expression is elevated in endometrial adenocarcinoma tissues compared with normal proliferative phase endometrium and is localised to the glandular and vascular cells. Using FPS cells, we show that PGF2α-FP signalling upregulates ADAMTS1 expression via a calmodulin-NFAT-dependent pathway and this promotes epithelial cell invasion through ECM and inhibits endothelial cell proliferation. Furthermore, we show that CM from FPS cells regulates endothelial cell ADAMTS1 expression in a rapid biphasic manner. Using RNA interference we show that endothelial cell ADAMTS1 also negatively regulates cellular proliferation.</p> <p>Conclusions</p> <p>These data demonstrate elevated ADAMTS1 expression in endometrial adenocarcinoma. Furthermore we have highlighted a mechanism whereby FP receptor signalling regulates epithelial cell invasion and endothelial cell function via the PGF_2α-FP receptor mediated induction of ADAMTS1.</p

Disparate Impact of Butyroyloxymethyl Diethylphosphate (AN-7), a Histone Deacetylase Inhibitor, and Doxorubicin in Mice Bearing a Mammary Tumor

The histone deacetylase inhibitor (HDACI) butyroyloxymethyl diethylphosphate (AN-7) synergizes the cytotoxic effect of doxorubicin (Dox) and anti-HER2 on mammary carcinoma cells while protecting normal cells against their insults. This study investigated the concomitant changes occurring in heart tissue and tumors of mice bearing a subcutaneous 4T1 mammary tumor following treatment with AN-7, Dox, or their combination. Dox or AN-7 alone led to inhibition of both tumor growth and lung metastases, whereas their combination significantly increased their anticancer efficacy and attenuated Dox- toxicity. Molecular analysis revealed that treatment with Dox, AN-7, and to a greater degree, AN-7 together with Dox increased tumor levels of γH2AX, the marker for DNA double-strand breaks and decreased the expression of Rad51, a protein needed for DNA repair. These events culminated in increased apoptosis, manifested by the appearance of cytochrome-c in the cytosol. In the myocardium, Dox-induced cardiomyopathy was associated with an increase in γH2AX expression and a reduction in Rad51 and MRE11 expression and increased apoptosis. The addition of AN-7 to the Dox treatment protected the heart from Dox insults as was manifested by a decrease in γH2AX levels, an increase in Rad51 and MRE11 expression, and a diminution of cytochrome-c release. Tumor fibrosis was high in untreated mice but diminished in Dox- and AN-7-treated mice and was almost abrogated in AN-7+Dox-treated mice. By contrast, in the myocardium, Dox alone induced a dramatic increase in fibrosis, and AN7+Dox attenuated it. The high expression levels of c-Kit, Ki-67, c-Myc, lo-FGF, and VEGF in 4T1 tumors were significantly reduced by Dox or AN-7 and further attenuated by AN-7+Dox. In the myocardium, Dox suppressed these markers, whereas AN-7+Dox restored their expression. In conclusion, the combination of AN-7 and Dox results in two beneficial effects, improved anticancer efficacy and cardioprotection

Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis.

Fibroblast growth factors (FGFs) are a family of heparin-binding growth factors. FGFs exert their pro-angiogenic activity by interacting with various endothelial cell surface receptors, including tyrosine kinase receptors, heparan-sulfate proteoglycans, and integrins. Their activity is modulated by a variety of free and extracellular matrix-associated molecules. Also, the cross-talk among FGFs, vascular endothelial growth factors (VEGFs), and inflammatory cytokines/chemokines may play a role in the modulation of blood vessel growth in different pathological conditions, including cancer. Indeed, several experimental evidences point to a role for FGFs in tumor growth and angiogenesis. This review will focus on the relevance of the FGF/FGF receptor system in adult angiogenesis and its contribution to tumor vascularization

Burnout and general health among nurses during Covid-19 outbreak. A cross sectional study in a Northern Italy hospital

Aim. To analyze the prevalence of Burnout syndrome and general health (GH) status among nurses in a Northern Italian hospital during COVID-19 outbreak and establish associations with socio-demographic factors. Methods. A descriptive correlational research was conducted in a Northern Italy hospital, in Lecco. 200 nurses were selected through the stratified randomized sampling method using their personnel codes. Three questionnaires were administered to analyze personal data, Burnout and General health status. Results. The useful and comprehensive questionnaires for our study came from 131 nurses, 80 (61.1%) were females. Nurses who experienced Burnout displayed symptoms of emotional exhaustion numbered 62 (47.3%), symptoms of depersonalization were evident in 63 (48.1%), and symptoms of reduced personal accomplishment (RPA) were seen in 64 (48.8%). Result from General Health Questionnaire observed moderate disorder related to work in a Covid department (p &lt;.001), and related to the age of respondents (p= .017). Regression analysis indicated a positive correlation between Burnout and Anxiety and Sleep disorder (β= 0.221, t= 2.2, p= .003) and Depression symptoms (β= 0.331, t= 3.5 p&lt; .001). Conclusion. Current results showed that Burnout is related to GH. Nurses have experienced a substantial increase in Burnout when managing COVID-19 patients.Scopo. Analizzare la prevalenza della sindrome da Burnout e lo stato di salute generale tra gli infermieri di un ospedale del Nord Italia durante la pandemia da COVID-19 e stabilire i livelli di relazione con i fattori socio-demografici. Metodi. Una ricerca correlazionale descrittiva è stata condotta in un ospedale del Nord Italia, Lecco. 200 infermieri sono stati selezionati attraverso il metodo di campionamento randomizzato stratificato utilizzando i loro codici personali. Tre questionari sono stati somministrati per analizzare dati anagrafici, Burnout e stato generale di salute. Risultati. I questionari utili per il nostro studio provenivano da 131 infermieri, 80 (61.1%) erano donne. Hanno sperimentato il Burnout con sintomi di esaurimento emotivo 62 infermieri (47.3%), sintomi di depersonalizzazione erano evidenti in 63 infermieri (48.1%) e sintomi di ridotta realizzazione personale sono stati osservati in 64 infermieri (48.8%). Il risultato del questionario sulla salute generale ha mostrato disturbi moderati correlati al lavoro in un reparto Covid (p &lt;.001) e in relazione all'età anagrafica (p= .017). L'analisi di regressione ha indicato una correlazione positiva tra Burnout e ansia e disturbo del sonno (β= 0.221, t= 2.2, p= .003) e con i sintomi di depressione (β= 0.331, t= 3.5 p&lt; .001). Conclusioni. I risultati attuali hanno mostrato che il Burnout è correlato a tutti gli aspetti del GH. Gli infermieri hanno sperimentato un sostanziale aumento del Burnout durante la gestione dei pazienti affetti da COVID-19

Sintomi Burnout-correlati tra il personale sanitario italiano di Terapia Intensiva durante l’emergenza COVID-19. Indagine conoscitiva multicentrica

AIM: to analyze the prevalence of Burnout defined by the MBI-GS among Italian Intensive Care (ICU) staff during the COVID-19 outbreak.&nbsp; METHOD: a multicentric study was conducted. A sample of 197 ICU health professionals (135 nurses and 62 physicians) participated in the study. Between 25 March and 15 May 2020, the Maslach Burnout Inventory-General Survey (MBI-GS) questionnaire was made available online by using the Google Forms platform in order to detect and measure the severity ofBurnout Syndrome (BOS).&nbsp; RESULTS: BOS-related symptoms (medium or high score) for individual MBI-GS domains have been identified in at least 69% of ICU healthcare professionals. Ninety-eight healthcare professionals (49.7%) had a moderate-high risk of emotional exhaustion, 108 (54.8%) ofdepersonalization, and 102 (51.8%) of reduced professional accomplishment. A high risk of emotional exhaustion (27.4% vs 8.1%, p = 0.002), a moderate risk of depersonalization(56.3% vs 32.2%, p = 0.0017) and a moderate risk for reduced professional accomplishment (60.7% vs 24.2%, p &lt;0.001) were observed among nursing staff. A strong association between increase in age and increase of the Burnout risk in ICU’s staff was observed (F=12.226; p &lt;0.001).&nbsp; CONCLUSIONS: the results suggest that ICU staff during the coronavirus pandemic, had high levels of work-related suffering and were at risk of physical and emotional exhaustion. However, further research should be undertaken to establish causal relationships between BOS and personal and environmental risk factors among healthcare professionals in relation to the COVID-19 outbreak.SCOPO: analizzare la prevalenza del Burnout definito dal MBI-GS tra il personale sanitario diTerapia Intensiva (TI) durante l’emergenza COVID-19.&nbsp; METODO: è stato condotto uno studio trasversale multicentrico. Un campione composto da197 sanitari (135 infermieri e 62 Medici) ha partecipato allo studio. Tra il 25 Marzo e il 15Maggio 2020, il questionario Maslach Burnout Inventory-General Survey (MBI-GS), è statoinviato online tramite la piattaforma Google Forms al fine di rilevare e misurare la gravità della Sindrome di Burnout (BOS).&nbsp; RISULTATI : i sintomi BOS-correlati (punteggio medio o alto) per i singoli domini della MBI-GS sono stati identificati in almeno il 69% dei sanitari. Novantotto sanitari (49.7%) presentavano un rischio medio-alto di esaurimento emotivo, 108 (54.8%) di depersonalizzazione e 102 (51.8%) di ridotta realizzazione personale. Un rischio alto di esaurimento emotivo (27.4% vs 8.1%, p= 0.002), un rischio moderato di depersonalizzazione (56.3% vs 32.2%, p= 0.0017) e un rischio moderato per la ridotta realizzazione personale (60.7% vs 24.2%, p&lt; 0.001) è stato maggiormente osservato tra il personale infermieristico. Dalla relazione tra Burnout ed età anagrafica, è stata osservata una forte associazione tra aumento dell’età e aumento del rischio di Burnout severo (F=12.226; p&lt;0.001) in tutto il personale intervistato.&nbsp; CONCLUSIONI: i risultati suggeriscono come il personale sanitario durante l’emergenza abbia avuto alti livelli di sofferenza lavorativa e sia stato a rischio di esaurimento fisico ed emotivo. Tuttavia ulteriori ricerche dovrebbero essere intraprese per stabilire relazioni causali tra BOS e fattori di rischio personale e ambientale tra gli operatori sanitari in relazione all’esperienza COVID-19.&nbsp

[Nosocomial infections during the COVID-19 outbreak. Observational study in an Italian ICU]

Introduction. Infections are common among ICU patients. Aim. The pur- pose of this study is to examine the incidence of nosoco- mial infections among patients admitted to the ICU with SARS-CoV-2 infection. Methods. A prospective observatio- nal study in adults with confirmed SARS-CoV-2 infection requiring intensive care unit (ICU) admission was performed. From May 2020 to October 2021, a total of 109 admitted patients were included. Results. The incidence rate of new infections was 39.4%. The main infections observed were multidrug-resistant germs infections (39.5%), catheter-rela- ted blood infections(24.4%), pneumonia (VAP)(18.6%), and urinary tract infections (17.4%). The overall mortality rate was 32.1% (n= 35) and was significantly higher in patients who had a new infection during hospitalization (n= 26/43, 60.4%) than in patients who did not have a new infection (n= 9/66, 13.6%) (RR = 4.43; 95% CI = 2.31-8.52; p <.001). Conclusions. Our data suggest that secondary infections are associated with a longer duration of mechanical ventilation and hospital stay and may negatively impact patient survi- val. However, larger studies are needed

Thrombospondin 1 as a scavenger for matrix-associated fibroblast growth factor 2

The antiangiogenic factor thrombospondin 1 (TSP-1) binds with high affinity to several heparin-binding angiogenic factors, including fibroblast growth factor 2 (FGF-2), vascular endothelial growth factor (VEGF), and hepatocyte growth factor/scatter factor (HGF/SF). The aim of this study was to investigate whether TSP-1 affects FGF-2 association with the extracellular matrix (ECM) and its bioavailability. TSP-1 prevented the binding of free FGF-2 to endothelial cell ECM. It also promoted the mobilization of matrix-bound FGF-2, generating a TSP-1/FGF-2 complex. The region of TSP-1 responsible for these activities was located within the 140-kDa antiangiogenic and FGF-2 binding fragment, whereas the 25-kDa heparin-binding fragment was inactive. Matrix-released FGF-2/TSP-1 complex had a reduced ability to bind to and induce proliferation of endothelial cells. TSP-1 depleted the ECM laid by FGF-2-overproducing tumor cells of its FGF-2-dependent mitogenic activity for endothelial cells. Besides FGF-2, TSP-1 also inhibited VEGF and HGF/SF binding to the ECM and mobilized them from the ECM. Our study shows that TSP-1 acts as a scavenger for matrix-associated angiogenic factors, affecting their location, bioavailability, and function

Long-term effects of Coronavirus 2 infection after intensive care: a prospective study

While the multi-organ manifestations of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection are now well-documented, the potential long-term implications of these manifestations remain to be uncovered. The aim was to study the level and predictors of post-traumatic stress, anxiety and depression symptoms, quality of life and functional disability in COVID-19 survivors during the first year post intensive care unit (ICU) discharge